Current evidence indicates that morphine and related opiates possess the ability to alter the synthesis, storage, release and/or receptor actions of endogenous neurotransmitters, hormones, and modulator autacoids in the intestine. These actions of the opiates account for many of their complicated intestinal motor effects and result ultimately in failure of propulsion. Experiments to date indicate that the intestinal spasm brought about by narcotic drugs is due in part to release of endogenous 5-hydroxytryptamine (5-HT). The 5-HT may be released from an intramural neuron under the influence of adenosine triphosphate (ATP) and which is exquisitely sensitive to beta adrenergic amines. The purposes of this investigation are (1) to explore further the role of 5-HT as a mediator of opiate effects in the intestine, (2) to identify those motor components of morphine action which cause constipation, (3) to examine the modulatory effects of adrenergic amines and cyclic AMP on morphine action, (4) to determine whether ATP or related neuromodulatory substances participate in responses to morphine, and (5) to establish optimal pharmacological means for selective inhibition of intestinal responses to opiates. These studies will be conducted primarily in dog isolated intestinal segments, in dog intestine in situ, and on rat intestinal propulsion in vivo. These studies will help define the mechanisms of opiate actions on the intestine and will provide the pharmacological basis for more rational therapeutic use of the potent analgesic drugs.